Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2

ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6. doi: 10.1021/ml3003346. eCollection 2012 Dec 13.


The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.

Keywords: EZH2; Epigenetics; H3K27me3; PRC2; SAM-competitive inhibitor; methyltransferase.